Duloxetine alcohol (3) is an important precursor in the preparation of duloxetine (4) (cf. scheme 1), which is sold under the trade name Cymbalta® inter alia as an antidepressant.

The intermediate (TACA) (2) that arises can be prepared with the help of a dehydrogenase (cf. WO2005/033094). For example, the phenylethanol dehydrogenase EbN1 from Azoarcus sp. (newer name Aromatoleum aromaticum) (cf. Höffken et al., Biochemistry, vol. 45, No. 1, 2006) reduces the chloroketone 3-chloro-1-(thienyl-2-yl)-propan-1-one (1) to the corresponding chloroalcohol (1S)-3-chloro-1-(thienyl-2-yl)-propan-1-ol (2), analogously to a Meerwein-Ponndorf reduction. For this, the dehydrogenase requires the cofactor nicotinamide-adenine dinucleotide (NADH), which produces the necessary reduction equivalents. This expensive cofactor can be regenerated with the help of a secondary “sacrificial alcohol” (e.g. 2-propanol or 2-butanol), during which the corresponding ketone (e.g. acetone or 2-butanone) is formed. Relatively long-chain alcohols are preferred by the enzyme here, but are also considerably more expensive. For this reason, 2-butanol is used as sacrificial alcohol (cf. scheme 2) (cf. also WO2006/072465).

The wild-type enzyme EbN1 and expression systems that can be used for its expression are described in WO2005/108590 and WO2006/094945.